High Rates of Tuberculosis in Patients Accessing HAART in Rural South Africa – Implications for HIV and TB Treatment Programs Kogieleum Naidoo on behalf of Quarraisha Abdool Karim, Ambika Bhushan, Kasavan Naidoo, Nonhlanhla Yende-Zuma, Patricia K Mchunu, Janet Frohlich, Farina Karim, Michele Upfold, Paul Kocheleff and Salim S Abdool Karim Abstract no. TUPDB0101

1.1 million HIV associated TB cases and deaths among TB-HIV co-infected patients, in 2010 Evidence supports TB screening and diagnosis, and HAART initiation early during TB therapy in co-infected patients Burden of undiagnosed TB at HAART initiation and number of new TB cases diagnosed during HAART in settings with a high HIV and TB burden not fully measured Study aim: To measure TB prevalence and incidence rates and impact on clinical outcomes among rural patients accessing HAART in a TB - HIV endemic setting Background

Prospective cohort study among 969 HIV-positive patients initiating HAART, conducted between January 2007 and December 2010 HAART eligibility included confirmed HIV status, CD4+ count < 200 cells/mm 3, or presence of WHO stage 4 condition TB was diagnosed based on a positive TB symptom screen; TB smear microscopy; and diagnostic radiology. Culture and drug susceptibility testing was limited Tuberculin Skin Testing and isoniazid preventive therapy (IPT) was not available during the study period Methods

Study definitions: – ‘prevalent TB’ on TB treatment at HAART initiation. –‘Incident TB’ new TB cases diagnosed after HAART initiation, –Incident TB was further classified into “unmasked TB” defined as a new TB diagnosis within 3 months of HAART initiation, and –“incident TB” defined as a new TB diagnosis occurring between 4 and 24 months post HAART initiation

TB prevalenceOverall TB incidence *Incidence of “unmasked” TB **Incident TB Baseline CD4+ count (cells/mm 3 ) Patients with prevalent TB/n TB Prevalen ce (95%CI) Patients with incident TB/n Numbe r of person years Incidence rate per 100 person- years (95% CI) Patients with incident TB/person years Incidence rate per 100 person- years (95% CI) Patients with incident TB/pers on years Incidence rate per 100 person- years (95% CI) All patients173/ (15.5 to 20.4) 54/ (3.3 to 5.8) 21/ (7.1 to 17.5.) 32/ (2.2 to 4.6) Missing17/ (12.3 to 30.0) 6/ (2.4 to 14.4) 4/ (7.3 to 68.8) 2/ (0.3 to 9.6) CD4+ count <50/ mm 3 47/ (19.2 to 32.1) 12/ (2.7 to 9.3) 3/ (2.0 to 28.2) 9/ (2.1 to 8.8) CD4+ count /mm 3 87/ (13.3 to 19.7) 26/ (2.5 to 5.5) 12/ (5.9 to 20.1) 14/ (1.3 to 4.0) CD4+ count >200/mm 3 22/ (9.0 to 20.2) 10/ (2.4 to 9.0) 2/ (0.7 to 21.8) 8/ (2.0 to 9.2) Results: Baseline CD4+ count specific TB prevalence and incidence

Unacceptably high TB incidence rates, in a rural HAART program in a TB HIV endemic setting –irrespective of baseline immunologic status of patients at HAART initiation, –duration on HAART –reflecting on-going susceptibility to TB, and on-going TB transmission High rates of prevalent TB especially among patients with CD4< 50 cells/mm 3 Findings highlight the need for enhanced TB screening and diagnosis, and need for programmatic implementation of TB preventive therapy especially among HIV infected patients in TB endemic settings Acknowledgement Financial support for CAPRISA was from the National Institute of Allergy and infectious Disease (NIAID), National Institutes of Health (NIH) (grant# AI51794); patient care and treatment has been supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centres for Disease Control and Prevention, grant number 1U2GPS001350; Dr Naidoo was supported by the Columbia University-Southern African Fogarty AIDS International Training and Research Program grant# D43TW Conclusion